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Resource Balance Analysis (RBA) is a framework for predicting steady-state cellular growth under resource constraints. However, classical RBA formulations are static and do not capture the dynamic regulation of biosynthetic resources or macromolecular turnover, which is particularly important in eukaryotic cells. In this work, we propose a dynamic extension of eukaryotic RBA based on an optimal control formulation. Cellular growth is modeled as the result of a time-dependent allocation of translational capacity between metabolic enzymes and macromolecular machinery, aimed at maximizing biomass accumulation over a finite time horizon. Using Pontryagin's Maximum Principle, we characterize optimal allocation strategies and show that steady-state RBA solutions arise as limiting regimes of the dynamic problem.
We investigate synchronization and metachronal-wave formation in a one-dimensional array of eukaryotic flagella using an elastohydrodynamic model. In contrast to a two-flagellum system, where only in-phase synchronization is stable, larger arrays are found to support stable metachronal waves with finite phase differences. Direct numerical simulations show that metachronal waves appear with increasing probability as the number of flagella increases. To explain this many-body effect, we construct a phase description for the array from that of the pair problem and analyze the stability of phase-locked states with nearest-neighbor hydrodynamic coupling. The analysis shows that increasing system size enlarges the set of stable phase-locked modes, thereby promoting metachronal-wave selection. A continuum description further relates these collective states to advection and diffusion of the phase-difference field. These results provide a simple theoretical framework for understanding how hydrodynamic interactions generate robust metachronal waves in flagellar arrays.
In eukaryotic cell chemotaxis, cells extend and retract transient actin-driven protrusions at their membrane that facilitate both the detection of external chemical gradients and directional movement via the formation of focal adhesions with the extracellular matrix. Although extensive experimental work has detailed how cellular protrusions and morphology vary under different environmental conditions, the mechanistic principles linking protrusive activity to these factors remain poorly understood. Here, we model the extension of actin-based protrusions in chemotaxis as an optimisation problem, wherein cells balance the detection of chemical gradients with the energetic cost of protrusion formation. Our model, built on the assumption of energy minimisation, provides a framework that successfully reproduces experimentally observed patterns of protrusive activity across a range of biological systems and environmental conditions, suggesting that energetic efficiency may underpin the morphology and chemotactic behaviour of motile eukaryotic cells. Additionally, we leverage the model to generate novel predictions regarding cellular responses to other, experimentally untested environmenta
Understanding the interplay among processes that occur over different timescales is a challenging issue in the physics of systems regulation. In gene regulation, the timescales for changes in chromatin states can differ from those for changes in the concentration of product protein, raising questions about how to understand their coupled dynamics. In this study, we examine the effects of these different timescales on eukaryotic gene regulation using a stochastic model that describes the landscapes and probability currents of nonequilibrium fluctuations.This model shows that slow, nonadiabatic transitions of chromatin states significantly impact gene-regulation dynamics. The simulated circular flow of the probability currents indicates a maximum entropy production when the rates of chromatin-state transitions are low in the intensely nonadiabatic regime. In the mildly nonadiabatic regime, this circular flow fosters hysteresis, suggesting that changes in chromatin states precede changes in transcription activity. Furthermore, calculations using a model of a circuit involving three core genes in mouse embryonic stem cells illustrate how the timescale difference can tune fluctuations i
Eukaryotic cells generally sense chemical gradients using the binding of chemical ligands to membrane receptors. In order to perform chemotaxis effectively in different environments, cells need to adapt to different concentrations. We present a model of gradient sensing where the affinity of receptor-ligand binding is increased when a protein binds to the receptor's cytosolic side. This interior protein (allosteric factor) alters the sensitivity of the cell, allowing the cell to adapt to different ligand concentrations. We propose a reaction scheme where the cell alters the allosteric factor's availability to adapt the average fraction of bound receptors to 1/2. We calculate bounds on the chemotactic accuracy of the cell, and find that the cell can reach near-optimal chemotaxis over a broad range of concentrations. We find that the accuracy of chemotaxis depends strongly on the diffusion of the allosteric compound relative to other reaction rates. From this, we also find a trade-off between adaptation time and gradient sensing accuracy.
Following genetic ancestry in eukaryote populations poses several open problems due to sexual reproduction and recombination. The history of extant genetic material is usually modeled backwards in time, but tracking chromosomes at a large scale is not trivial, as successive recombination events break them into several segments. For this reason, the behavior of the distribution of genetic segments across the ancestral population is not fully understood. Moreover, as individuals transmit only half of their genetic content to their offspring, after a few generations, it is possible that ghosts arise, that is, genealogical ancestors that transmit no genetic material to any individual. While several theoretical predictions exist to estimate properties of ancestral segments or ghosts, most of them rely on simplifying assumptions such as an infinite population size or an infinite chromosome length. It is not clear how well these results hold in a finite universe, and current simulators either make other approximations or cannot handle the scale required to answer these questions. In this work, we use an exact back-in-time simulator of large diploid populations experiencing recombination t
Eukaryotic swimming cells such as spermatozoa, algae or protozoa use flagella or cilia to move in viscous fluids. The motion of their flexible appendages in the surrounding fluid induces propulsive forces that balance with the viscous drag on the cells and lead to a directed swimming motion. Here, we use our recently built database of cell motility (BOSO-Micro) to investigate the extent to which the shapes of eukaryotic swimming cells may be optimal from a hydrodynamic standpoint. We first examine the morphology of flexible flagella undergoing waving deformation and show that their amplitude-to-wavelength ratio is near the one predicted theoretically to optimise the propulsive efficiency of active filaments. Next, we consider ciliates, for which locomotion is induced by the collective beating of short cilia covering their surface. We show that the aspect ratio of ciliates are close to the one predicted to minimise the viscous drag of the cell body. Both results strongly suggest a key role played by hydrodynamic constraints, in particular viscous drag, in shaping eukaryotic swimming cells.
Annotating the structure of protein-coding genes represents a major challenge in the analysis of eukaryotic genomes. This task sets the groundwork for subsequent genomic studies aimed at understanding the functions of individual genes. BRAKER and Galba are two fully automated and containerized pipelines designed to perform accurate genome annotation. BRAKER integrates the GeneMark-ETP and AUGUSTUS gene finders, employing the TSEBRA combiner to attain high sensitivity and precision. BRAKER is adept at handling genomes of any size, provided that it has access to both transcript expression sequencing data and an extensive protein database from the target clade. In particular, BRAKER demonstrates high accuracy even with only one type of these extrinsic evidence sources, although it should be noted that accuracy diminishes for larger genomes under such conditions. In contrast, Galba adopts a distinct methodology utilizing the outcomes of direct protein-to-genome spliced alignments using miniprot to generate training genes and evidence for gene prediction in AUGUSTUS. Galba has superior accuracy in large genomes if protein sequences are the only source of evidence. This chapter provides
The eukaryotic protein synthesis process entails intricate stages governed by diverse mechanisms to tightly regulate translation. Translational regulation during stress is pivotal for maintaining cellular homeostasis, ensuring the accurate expression of essential proteins crucial for survival. This selective translational control mechanism is integral to cellular adaptation and resilience under adverse conditions. This review manuscript explores various mechanisms involved in selective translational regulation, focusing on mRNA-specific and global regulatory processes. Key aspects of translational control include translation initiation, which is often a rate-limiting step, and involves the formation of the eIF4F complex and recruitment of mRNA to ribosomes. Regulation of translation initiation factors, such as eIF4E, eIF4E2, and eIF2, through phosphorylation and interactions with binding proteins, modulates translation efficiency under stress conditions. This review also highlights the control of translation initiation through factors like the eIF4F complex and the ternary complex and also underscores the importance of eIF2α phosphorylation in stress granule formation and cellular
The biochronometers used to keep time in eukaryotes include short-period biochronometer (SPB) and long-period biochronometer (LPB). Because the circadian clock reflects the biological time rhythm of a day, it is considered as SPB. Telomere shortening, which reflects the decreasing of telomere DNA length of chromosomes with the increase of cell division times, can be used to time the lifespan of organisms, so it is regarded as LPB. It is confirmed that SPB and LPB exist in most eukaryotes, and it is speculated that SPB and LPB are closely related. In this paper, based on existing studies, it is speculated that SPB and LPB of most eukaryotes can be co-attenuated with cell division in the process of aging. Due to the attenuated phenomenon of key components in the biochronometers during the growth and development of organisms, the biochronometers attenuate with the aging. Based on existing research results, it is preliminarily determined that the biochronometers can be rebuilt in the co-attenuated process. When the key components of biochronometers are reversed and increased in the organism, it can lead to the reversal of biochronometers, which further leads to the phenomenon of biolog
In order to study unknown proteins on a large scale, a reference system has been set up for the three major eukaryotic lineages, built with 36 proteomes as taxonomically diverse as possible. Proteins from 362 eukaryotic proteomes with no known homologue in this set were then analyzed, focusing noteworthy on singletons, that is, on unknown proteins with no known homologue in their own proteome. Consistently, according to Uniprot, for a given species, no more than 12% of the singletons thus found are known at the protein level. Also, since they rely on the information found in the alignment of homologous sequences, predictions of AlphaFold2 for their tridimensional structure are usually poor. In the case of metazoan species, the number of singletons seems to increase as a function of the evolutionary distance from the reference system. Interestingly, no such trend is found in the cases of viridiplantae and fungi, as if the timescale on which singletons are added to proteomes were different in metazoa and in other eukaryotic kingdoms. In order to confirm this phenomenon, further studies of proteomes closer to those of the reference system are however needed.
RNA-guided gene editing based on the CRISPR-Cas system is currently the most effective genome editing technique. Here, we report that the SviCas3 from the subtype I-B-Svi Cas system in Streptomyces virginiae IBL14 is an RNA-guided and DNA-guided DNA endonuclease suitable for the HDR-directed gene and/or base editing of eukaryotic cell genomes. The genome editing efficiency of SviCas3 guided by DNA is no less than that of SviCas3 guided by RNA. In particular, t-DNA, as a template and a guide, does not require a proto-spacer-adjacent motif, demonstrating that CRISPR, as the basis for crRNA design, is not required for the SviCas3-mediated gene and base editing. This discovery will broaden our understanding of enzyme diversity in CRISPR-Cas systems, will provide important tools for the creation and modification of living things and the treatment of human genetic diseases, and will usher in a new era of DNA-guided gene editing and base editing.
Eukaryotic cell motility is crucial during development, wound healing, the immune response, and cancer metastasis. Some eukaryotic cells can swim, but cells more commonly adhere to and crawl along the extracellular matrix. We study the relationship between hydrodynamics and adhesion that describe whether a cell is swimming, crawling, or combining these motions. Our simple model of a cell, based on the three-sphere swimmer, is capable of both swimming and crawling. As cell-matrix adhesion strength increases, the influence of hydrodynamics on migration diminish. Cells with significant adhesion can crawl with speeds much larger than their nonadherent, swimming counterparts. We predict that, while most eukaryotic cells are in the strong-adhesion limit, increasing environment viscosity or decreasing cell-matrix adhesion could lead to significant hydrodynamic effects even in crawling cells. Signatures of hydrodynamic effects include dependence of cell speed on the medium viscosity or the presence of a nearby substrate and the presence of interactions between noncontacting cells. These signatures will be suppressed at large adhesion strengths, but even strongly adherent cells will generat
All organisms, fundamentally, are made from the same raw material, namely the elements of the periodic table. Biochemical diversity is achieved with how these elements are utilized, for what purpose and in which physical location. Determining elemental distributions, especially those of trace elements that facilitate metabolism as cofactors in the active centers of essential enzymes, can determine the state of metabolism, the nutritional status or the developmental stage of an organism. Photosynthetic eukaryotes, especially algae, are excellent subjects for quantitative analysis of elemental distribution. These microbes utilize unique metabolic pathways that require various trace nutrients at their core to enable its operation. Photosynthetic microbes also have important environmental roles as primary producers in habitats with limited nutrient supply or toxin contaminations. Accordingly, photosynthetic eukaryotes are of great interest for biotechnological exploitation, carbon sequestration and bioremediation, with many of the applications involving various trace elements and consequently affecting their quota and intracellular distribution. A number of diverse applications were de
Methods for evaluating the quality of genomic and metagenomic data are essential to aid genome assembly and to correctly interpret the results of subsequent analyses. BUSCO estimates the completeness and redundancy of processed genomic data based on universal single-copy orthologs. Here we present new functionalities and major improvements of the BUSCO software, as well as the renewal and expansion of the underlying datasets in sync with the OrthoDB v10 release. Among the major novelties, BUSCO now enables phylogenetic placement of the input sequence to automatically select the most appropriate dataset for the assessment, allowing the analysis of metagenome-assembled genomes of unknown origin. A newly-introduced genome workflow increases the efficiency and runtimes especially on large eukaryotic genomes. BUSCO is the only tool capable of assessing both eukaryotic and prokaryotic species, and can be applied to various data types, from genome assemblies and metagenomic bins, to transcriptomes and gene sets.
This paper proposes that eukaryotic cells, under severe genotoxic stress, can commit genoautotomy (genome 'self-injury') that involves cutting and releasing single-stranded DNA (ssDNA) fragments from double-stranded DNA and leaving ssDNA gaps in the genome. The ssDNA gaps could be easily and precisely repaired later. The released ssDNA fragments may play some role in the regulation of cell cycle progression. Taken together, genoautotomy causes limited nonlethal DNA damage, but prevents the whole genome from lethal damage, and thus should be deemed as a eukaryotic cellular defence response to genotoxic stress.
Eukaryotic adaptation pathways operate within wide-ranging environmental conditions without stimulus saturation. Despite numerous differences in the adaptation mechanisms employed by bacteria and eukaryotes, all require energy consumption. Here, we present two minimal models showing that expenditure of energy by the cell is not essential for adaptation. Both models share important features with large eukaryotic cells: they employ small diffusible molecules and involve receptor subunits resembling highly conserved G-protein cascades. Analyzing the drawbacks of these models helps us understand the benefits of energy consumption, in terms of adjustability of response and adaptation times as well as separation of cell-external sensing and cell-internal signaling. Our work thus sheds new light on the evolution of adaptation mechanisms in complex systems.
Several orders of magnitude typically separate the contour length of eukaryotic chromosomes and the size of the nucleus where they are confined. The ensuing topological constraints can slow down the relaxation dynamics of genomic filaments to the point that mammalian chromosomes are never in equilibrium over a cell's lifetime. In this opinion article, we revisit these out-of-equilibrium effects and discuss how their inclusion in physical models can enhance the spatial reconstructions of interphase eukaryotic genomes from phenomenological constraints collected during interphase.
Till now, in biological sciences, the term, transcription, mainly refers to DNA to RNA transcription. But our recently published experimental findings obtained from Plasmodium falciparum strongly suggest the existence of DNA to DNA transcription in the genome of eukaryotic cells, which could shed some light on the functions of certain noncoding DNA in the human and other eukaryotic genomes.
Genome length varies widely among organisms, from compact genomes of prokaryotes to vast and complex genomes of eukaryotes. In this study, we theoretically identify the evolutionary pressures that may have driven this divergence in genome length. We use a parameter-free model to study genome length evolution under selection pressure to minimize replication time and maximize information storage capacity. We show that prokaryotes tend to reduce genome length, constrained by a single replication origin, while eukaryotes expand their genomes by incorporating multiple replication origins. We propose a connection between genome length and cellular energetics, suggesting that endosymbiotic organelles, mitochondria and chloroplasts, evolutionarily regulate the number of replication origins, thereby influencing genome length in eukaryotes. We show that the above two selection pressures also lead to strict equalization of the number of purines and their corresponding base-pairing pyrimidines within a single DNA strand, known as Chagraff's second parity rule, a hitherto unexplained observation in genomes of nearly all known species. This arises from the symmetrization of replichore length, an